Patterns of glycogen turnover in liver characterized by computer modeling

We used a computer model of liver glycogen turnover to reexamine the data of Devos and Hers, who reported the time course of accumulation in and loss from glycogen of label originating in [1-14C]galactose injected at different times after the start of refeeding of 40-h fasted mice or rats. In the present study computer representation of individual glycogen molecules was utilized to account for growth and degradation of glycogen according to specific hypothetical patterns. Using this model we could predict the accumulation and localization within glycogen of labeled glucose residues and compare the predictions with the previously published data. We considered three specific hypotheses of glycogen accumulation during refeeding: 1) simultaneous, 2) sequential, and 3) accelerating growth. Hypothetical patterns of glycogen degradation were 1) ordered and 2) random degradation. The pattern of glycogen synthesis consistent with experimental data was a steadily increasing number of growing glycogen molecules, whereas during degradation glycogen molecules are exposed to degrading enzymes randomly, rather than in a specific reverse order of synthesis. These patterns predict the existence of a specific mechanism for the steadily increasing "seeding" of new glycogen molecules during synthesis.